Sodium Carbonate → tert-butyl 3-(4-amino-3-{4-[(5,7-dimethyl-1,3-benzoxazol-2-yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

The mixture of tert-butyl 3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate (0.6 g, 0.00135 mol), N-(5,7-dimethyl-1,3-benzoxazol-2-yl)-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine (0.59 g, 0.00162 mol), tetrakis(triphenylphosphine)palladium (0.078 g, 0.000068 mol) and sodium carbonate (0.36 g, 0.00338 mol) in ethylene glycol dimethyl ether (50 mL) and water (10 mL) was heated at 80° C. for 16 hours under an atmosphere of nitrogen. After cooled the mixture to the room temperature, more N-(5,7-dimethyl-1,3-benzoxazol-2-yl)-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine (0.24 g, 0.00066 mol), tetrakis(triphenylphosphine)palladium (0.078 g, 0.000068 mol) were added, and the mixture was stirred at 80° C. for 5 hours. The mixture was allowed to cool to ambient temperature, and the solvent was removed under the reduced pressure. The residue was partitioned between water and dichloromethane. The aqueous layer was extracted with dichloromethane (3×50 mL). The combined organic extracts were washed with water, saturated aqueous sodium bicarbonate solution, and brine, and dried over magnesium sulfate. The solvents were evaporated under the reduced pressure to leave a brownish oil which was purified by flash column chromatography on silica using 5%-25% isopropanol/dichloromethane as a mobile phase, and the product was triturated with N,N-dimethylformamide to give tert-butyl 3-(4-amino-3-{4-[(5,7-dimethyl-1,3-benzoxazol-2-yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate (0.28 g, 0.00051 mol). RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-95% acetonitrile-0.1M ammonium acetate over 10 min, 1 mL/min) Rt 11.9 min.

Provenance & Evidence